Lysozyme-like protein 7 (LYS-7) is a protist-type (Entamoeba-type) lysozyme that functions as a key antimicrobial effector in C. elegans innate immunity. Despite belonging to the glycosyl hydrolase family 25 and containing a Ch-type lysozyme domain, the protein lacks conserved catalytic residues and may not have enzymatic activity. LYS-7 is expressed in the intestine, rectal gland cells, and head neurons, and is strongly induced by various bacterial pathogens including S. marcescens, M. nematophilum, and S. typhimurium. Functional studies demonstrate that LYS-7 provides resistance against the Gram-positive bacterium B. thuringiensis and M. nematophilum, and the fungal pathogen C. neoformans. Intriguingly, lys-7 knockout animals show increased tolerance to S. typhimurium infection, revealing a complex immunological trade-off. LYS-7 expression is regulated by the p38 MAPK pathway and the DAF-2/DAF-16 insulin-like signaling pathway, with P. aeruginosa actively suppressing lys-7 expression as a virulence strategy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007165 signal transduction | IBA GO_REF:0000033 | REMOVE | Summary: This annotation from phylogenetic analysis (PANTHER) is questionable for lys-7. LYS-7 is a lysozyme-like protein that functions as an antimicrobial effector molecule. While lys-7 expression is regulated by signal transduction pathways (p38 MAPK, DAF-2/DAF-16 insulin signaling), the protein itself is not directly involved in signal transduction. LYS-7 is a downstream effector of these signaling pathways, not a component of the signaling cascade. Reason: LYS-7 is an antimicrobial effector molecule whose expression is regulated by signaling pathways, but it does not itself participate in signal transduction. The annotation likely results from phylogenetic inference that does not distinguish between regulators and effectors of signaling pathways. Supporting Evidence: PMID:18927620 We hypothesized that repression of immune effector expression, such as thn-2, spp-1, and lys-7, may represent a virulence mechanism used by P. aeruginosa to suppress host defenses. PMID:19023415 Deficiencies in GLA and SDA result in increased susceptibility to bacterial infection, which is associated with reduced basal expression of a number of immune-specific genes--including spp-1, lys-7, and lys-2--that encode antimicrobial peptides. file:worm/lys-7/lys-7-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0045087 innate immune response | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation supported by extensive experimental evidence. LYS-7 is one of the most studied lysozymes in C. elegans immunity. Multiple publications demonstrate its role in defense against bacterial and fungal pathogens including M. nematophilum, B. thuringiensis, and C. neoformans (PMID:16809667, PMID:21931778, PMID:21399680). The protein is induced by pathogen exposure and required for optimal host survival. Reason: Strong experimental support from multiple independent studies. LYS-7 is a core innate immune effector in C. elegans, with knockout mutants showing increased susceptibility to multiple pathogens. Supporting Evidence: PMID:21931778 We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens. PMID:21399680 The lysozyme LYS-7 has been well-described in C. elegans as an essential antimicrobial molecule |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: UniProt keyword-based annotation. This is a broad parent term of innate immune response (GO:0045087). The annotation is correct but more specific terms are available and annotated with experimental evidence. Reason: While a broad term, it is correct. The more specific child term GO:0045087 (innate immune response) is also annotated with stronger evidence, so this IEA annotation provides redundant coverage that is acceptable. Supporting Evidence: PMID:21931778 We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens. |
| GO:0003796 lysozyme activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based annotation assigning lysozyme activity based on the presence of the glycosyl hydrolase 25 domain (IPR002053). However, the UniProt record explicitly notes that LYS-7 "Lacks conserved active site residues, suggesting it has no catalytic activity." While the protein belongs to the lysozyme family, it may not have functional lysozyme enzymatic activity. Reason: The protein contains a lysozyme domain but UniProt cautions that "Lacks conserved active site residues, suggesting it has no catalytic activity." No experimental evidence demonstrates that LYS-7 has lysozyme catalytic activity. The protein may function through a non-enzymatic mechanism. Supporting Evidence: UniProt:O16202 Lacks conserved active site residues, suggesting it has no catalytic activity. |
| GO:0006950 response to stress | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine learning annotation. This is a very broad term. While lys-7 is induced by pathogen stress, the more specific defense response terms (GO:0050829, GO:0050830, GO:0050832) are more appropriate and are already annotated with experimental evidence. Reason: While broad, this annotation is not incorrect. LYS-7 is indeed induced as part of the stress response to pathogen infection. More specific terms are also annotated, so this provides appropriate ontological coverage. Supporting Evidence: PMID:21931778 Lysozymes are small enzymes, which can cleave peptidoglycan, an essential component of bacterial cell walls. They are found in almost all groups of organisms and play important roles in both immunity and digestion |
| GO:0009253 peptidoglycan catabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based annotation derived from the glycosyl hydrolase 25 domain. Lysozymes typically cleave peptidoglycan in bacterial cell walls. However, since LYS-7 lacks conserved catalytic residues, this function may not apply. Reason: While typical lysozymes degrade peptidoglycan, the UniProt record notes that LYS-7 "Lacks conserved active site residues, suggesting it has no catalytic activity." Without experimental evidence of peptidoglycan degradation activity, this annotation is likely an over-annotation based on family membership rather than demonstrated function. Supporting Evidence: UniProt:O16202 Lacks conserved active site residues, suggesting it has no catalytic activity. |
| GO:0016998 cell wall macromolecule catabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based annotation, parent term of peptidoglycan catabolic process. Same concerns apply as for GO:0009253 - LYS-7 may lack enzymatic activity needed for this process. Reason: As LYS-7 lacks conserved catalytic residues and may not have enzymatic activity, assigning cell wall degradation activity is likely an over-annotation based on domain homology rather than demonstrated function. Supporting Evidence: UniProt:O16202 Lacks conserved active site residues, suggesting it has no catalytic activity. |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: UniProt keyword-based annotation. Duplicates the IBA annotation above but with weaker evidence. The annotation is correct and supported by experimental evidence from other annotations. Reason: Correct annotation, though redundant with the IBA annotation. LYS-7 is a well-established innate immune effector. Supporting Evidence: PMID:21931778 We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:16809667 Genomic clusters, putative pathogen recognition molecules, a... | ACCEPT | Summary: Experimental annotation from O'Rourke et al. 2006 studying M. nematophilum infection. lys-7 was induced by M. nematophilum infection and mutants showed enhanced susceptibility. M. nematophilum is a Gram-positive bacterium that infects the C. elegans rectum. Reason: Strong experimental evidence. The paper demonstrates that lys-7 is induced by M. nematophilum infection and is required for defense, with mutants showing more severe infection phenotypes (increased constipation, tail swelling, growth arrest). Supporting Evidence: PMID:16809667 We tested 41 of the induced genes for involvement in immunity using mutants or RNAi, finding that six of these are required for the swelling response and five are required more generally for defense. UniProt:O16202 Compared to wild-type, mutants grown in presence of bacterium M.nematophilum are more constipated, the tail swelling is increased, growth is slower and they are arrested at the L3 larval stage |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:22841995 Studies on Shigella boydii infection in Caenorhabditis elega... | ACCEPT | Summary: Experimental annotation from Kesika and Balamurugan 2012 studying Shigella infection. Shigella species are actually Gram-negative bacteria, not Gram-positive, making this specific annotation taxonomically incorrect. However, lys-7 does provide defense against genuine Gram-positive bacteria (M. nematophilum, B. thuringiensis), so the overall term is appropriate for this gene. Reason: While the specific reference (PMID:22841995) incorrectly applies this term to Shigella (which are Gram-negative), the annotation to GO:0050830 is nonetheless correct for lys-7 based on strong evidence from other studies with true Gram-positive bacteria (M. nematophilum, B. thuringiensis). The underlying annotation is correct; only this particular evidence line is taxonomically misapplied. Supporting Evidence: PMID:22841995 Increased mortality of mutant RB1285 by S. boydii and Shigella flexneri indicated the role of lys-7 during Shigella infection. PMID:21931778 We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens. |
| GO:0050832 defense response to fungus | IMP PMID:21399680 A two-gene balance regulates Salmonella typhimurium toleranc... | ACCEPT | Summary: Experimental annotation from Marsh et al. 2011. The study demonstrates that lys-7 knockout animals (ok1384) show severely reduced survival following exposure to the fungal pathogen Cryptococcus neoformans compared to wild-type. Reason: Strong experimental evidence. lys-7 knockout mutants are hypersusceptible to C. neoformans, demonstrating a protective role against fungal infection. The authors suggest this may be due to secondary chitinase activity exhibited by lysozymes. Supporting Evidence: PMID:21399680 In line with this prediction, a lys-7 knockout strain (ok1384) showed wild type brood size and longevity under non-infectious conditions PMID:21399680 Here we show that LYS-7 protects animals against C. neoformans-mediated killing, a function that is presumably attributable to the secondary chitinase (anti-fungal) activity exhibited by most lysozymes |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:18927620 Pseudomonas aeruginosa suppresses host immunity by activatin... | ACCEPT | Summary: Experimental annotation from Evans et al. 2008. The study shows that lys-7 expression is repressed by P. aeruginosa (a Gram-negative bacterium) as a virulence strategy, and that knockdown of lys-7 by RNAi enhances susceptibility to P. aeruginosa infection. Reason: The study demonstrates that lys-7 is required for defense against P. aeruginosa. RNAi knockdown of lys-7 enhances susceptibility to infection, and P. aeruginosa actively suppresses lys-7 expression as a virulence mechanism. Supporting Evidence: PMID:18927620 We hypothesized that repression of immune effector expression, such as thn-2, spp-1, and lys-7, may represent a virulence mechanism used by P. aeruginosa to suppress host defenses. PMID:18927620 Knockdown of thn-2, lys-7, and spp-1 by RNAi enhances the susceptibility of C. elegans to P. aeruginosa infection. |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:21931778 Protist-type lysozymes of the nematode Caenorhabditis elegan... | ACCEPT | Summary: Experimental annotation from Boehnisch et al. 2011 studying B. thuringiensis infection. The study demonstrates that lys-7 knockout mutants show decreased survival on pathogenic B. thuringiensis, and overexpression of lys-7 increases resistance. Reason: Strong experimental evidence from knockout and overexpression studies. lys-7(ok1384) knockout animals showed significantly decreased survival on B. thuringiensis B-18247, and transgenic overexpression of lys-7 increased survival, demonstrating a direct protective role. Supporting Evidence: PMID:21931778 Their knock-out led to decreased pathogen resistance in all three cases, while an increase in resistance was observed when two out of three tested genes were overexpressed in transgenic lines (lys-5, lys-7, but not lys-2). PMID:21931778 We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens. |
| GO:0045087 innate immune response | IMP PMID:19023415 Gamma-linolenic and stearidonic acids are required for basal... | ACCEPT | Summary: Experimental annotation from Nandakumar and Tan 2008. The study shows that lys-7 is one of the immune-specific genes whose basal expression requires GLA and SDA fatty acids and p38 MAPK pathway activity. Reduced lys-7 expression correlates with increased susceptibility to P. aeruginosa. Reason: The study demonstrates that lys-7 is a key immune effector gene required for basal innate immunity in C. elegans. Its expression is regulated by the p38 MAPK pathway and is essential for defense against bacterial infection. Supporting Evidence: PMID:19023415 Deficiencies in GLA and SDA result in increased susceptibility to bacterial infection, which is associated with reduced basal expression of a number of immune-specific genes--including spp-1, lys-7, and lys-2--that encode antimicrobial peptides. PMID:19023415 GLA and SDA are required to maintain basal activity of the p38 MAP kinase pathway, which plays important roles in protecting metazoan animals from infections and oxidative stress. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:19023415 Gamma-linolenic and stearidonic acids are required for basal... | ACCEPT | Summary: Experimental annotation from Nandakumar and Tan 2008. The study demonstrates that lys-7 is required for defense against P. aeruginosa (Gram-negative), with reduced expression leading to increased susceptibility. Reason: The study shows that reduced lys-7 expression in fat-3 mutants correlates with increased susceptibility to P. aeruginosa. This supports the role of lys-7 in defense against Gram-negative bacteria. Supporting Evidence: PMID:19023415 Deficiencies in GLA and SDA result in increased susceptibility to bacterial infection, which is associated with reduced basal expression of a number of immune-specific genes--including spp-1, lys-7, and lys-2 |
| GO:0050829 defense response to Gram-negative bacterium | IGI PMID:21399680 A two-gene balance regulates Salmonella typhimurium toleranc... | ACCEPT | Summary: Genetic interaction annotation from Marsh et al. 2011. The study reveals a complex genetic interaction between lys-7 and abl-1 in regulating immunity to S. typhimurium. Interestingly, lys-7 knockout animals are MORE resistant to S. typhimurium (a Gram-negative bacterium), not less. However, lys-7 does provide defense against other Gram-negative bacteria (P. aeruginosa), so the overall annotation is appropriate for the gene. Reason: While this specific reference shows lys-7 acts as a susceptibility factor for S. typhimurium (an immunological trade-off), the overall annotation to GO:0050829 is correct for lys-7 based on strong evidence of defense against P. aeruginosa from other studies (PMID:18927620, PMID:19023415). The S. typhimurium phenotype represents a pathogen-specific exception within an otherwise defensive role against Gram-negative bacteria. Supporting Evidence: PMID:21399680 Remarkably, however, lys-7 acts as a susceptibility factor for S. Typhimurium killing, as the loss of lys-7 more than doubles the median survival of Salmonella-challenged animals. PMID:18927620 Knockdown of thn-2, lys-7, and spp-1 by RNAi enhances the susceptibility of C. elegans to P. aeruginosa infection. |
| GO:0030246 carbohydrate binding | ISS UniProt:O16202 | NEW | Summary: Proposed new annotation based on structural inference. LYS-7 contains a Ch-type lysozyme domain (amino acids 53-273) which is a carbohydrate-binding domain. While catalytic activity may be absent due to missing active site residues, the domain structure suggests retention of carbohydrate binding capability. This may explain the antimicrobial function through non-enzymatic binding to bacterial or fungal cell wall components. Reason: LYS-7 has a Ch-type lysozyme domain that typically binds carbohydrates. Even without catalytic activity, binding to peptidoglycan or chitin components could provide antimicrobial function. This annotation captures the likely molecular function when enzymatic activity is uncertain. Supporting Evidence: UniProt:O16202 Belongs to the glycosyl hydrolase 25 family. PMID:21399680 a function that is presumably attributable to the secondary chitinase (anti-fungal) activity exhibited by most lysozymes |
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Download this section (compressed HTML)Q: Does LYS-7 have enzymatic activity given that it lacks conserved active site residues?
Experiment: Biochemical assay for lysozyme activity - Directly test whether purified LYS-7 protein has peptidoglycan-degrading or chitinase activity, given the absence of conserved catalytic residues.
Experiment: Structure-function analysis - Determine which domains/residues of LYS-7 are required for antimicrobial function to understand if it acts enzymatically or via binding/signaling.
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